Two near-infrared (NIR) contrast agents have been developed that are efficiently taken up by the thyroid and parathyroid glands following intravenous injection. These contrast agents were tested in rats and pigs, which showed that they could help distinguish the thyroid and parathyroid glands from surrounding tissue and from each other. These findings appeared in Nature Medicine (2015; doi:10.1038/nm.3728).

The thyroid is a butterfly shaped gland located in the front of the neck that controls the rate of many activities involved in metabolism. Directly behind the thyroid sit four parathyroid glands, which tightly control calcium levels in the blood; each is approximately the size of a grain of rice.

If the thyroid is not working properly, or if a tumor is present, surgery may be needed to remove all or part of the gland. While the thyroid and parathyroids can be located prior to surgery via ultrasound, once a patient is on the operating table surgeons have only their eyes and knowledge of anatomy to help them distinguish these important glands from other tissues in the body. Inability to do so can result in incomplete removal of the thyroid or inadvertent damage to the parathyroids, which can cause chronically low calcium levels.

“Proper identification of the thyroid and parathyroid glands during head and neck surgery is critical for avoiding accidental injury, but presents a significant challenge due to their small size and variations in location from patient to patient,” said Richard Conroy, PhD, director of the Division of Applied Science & Technology at the National Institute of Biomedical Imaging and Bioengineering.

“The innovative design and optimization of these contrast agents has the potential to lead to the development of other tissue-specific small molecule contrast agents. It's a great example of how investing in the development of new imaging technologies can help overcome existing challenges in medicine.”

Once injected intravenously, the new contrast agents are taken up by the thyroid and parathyroids, where they emit different wavelengths of NIR light. Although this light is invisible to the naked eye, it can be easily seen using FLARE, a specially designed NIR camera called. The FLARE camera shoots a color video of the surgical site and also captures the two NIR wavelengths to create a unique view in which the tissues that have taken up contrast agents glow brightly. In their experiments on rats and pigs, the researchers used FLARE to visualize the thyroid and parathyroid simultaneously.

The development of the contrast agents was led by John V. Frangioni, MD, PhD, and Hak Soo Choi, PhD, both of Harvard Medical School in Boston, Massachusetts. Chemical synthesis was performed at Georgia State University in Atlanta in the laboratory of Maged Henary, PhD. Frangioni is also CEO of Curadel, a company he started in 2014 with the purpose of developing NIR contrast agents and imaging systems to help surgeons identify glands, blood vessels, nerves, lymph nodes, and tumors during operations.

“We're giving surgeons the ability to find these structures through blood and through tissue, and in doing so, we're bringing surgery into the 21st century,” said Frangioni.